Abstract
The relationship between the acute toxicity and biologic fate of 1,1-dichloroethylene (1,1-DCE) was examined in fasted and fed male Sprague-Dawley rats given 200 mg 1,1-DCE/kg orally in a mineral oil, a corn oil, or an aqueous Tween-80 vehicle. Exhalation of unchanged 1,1-DCE by individual rats was monitored at selected 15-min intervals for 5 hr and all rats were sacrificed at 6 hr. The administrative vehicle affected the magnitude of liver injury in fasted rats; with mineral oil or corn oil, injury was massive [> 100-fold elevation of glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT)] whereas with the aqueous Tween-80 vehicle, injury was moderate t 15-fold elevation of GOT and GPT). In contrast, in all fed groups liver injury was slight (two- to threefold elevation of GOT and GPT). Rats with massive liver injury also had an ∼50-fold increase in plasma free hemoglobin and their kidneys exhibited numerous granular “heme” casts in Henle's loop without apparent degenerative changes in either glomeruli or tubular epithelium. No pathologic changes were observed in heart, lungs, spleen, adrenals, or duodenum. The administrative vehicle did not affect the total amount of 1,1-DCE exhaled, which was approximately half the given dose, nor did the vehicle affect the initial rapid phase of 1,1-DCE exhalation, which lasted ∼1 hr and had t 1 2 values ranging from 15 to 21 min for the fasted groups and from 10 to 13 min for the fed groups. In contrast, the later slow phase of 1,1-DCE exhalation was predictably affected by the administrative vehicle; t 1 2 values for the fasted and fed groups, respectively, were most prolonged with the poorly absorbed mineral oil vehicle (257 and 280 min), intermediate with the more digestable corn oil vehicle (73 and 103 min), and briefest with the more absorbable aqueous Tween vehicle (22 and 42 min). Further studies are needed to determine if the relative resistance of the fed animals to hepatic injury is due to the capacity of these animals to detoxify 1,1-DCE for a longer duration than the fasted animals.
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